Prostate cancer (CaP) is the most common malignancy and the second leading cause of cancer deaths in American men. The current clinical methods used for the detection of CaP are the serum prostate specific antigen (PSA) test, and the digital rectal examination (DRE) followed by biopsy, which is the gold standard for prostate cancer diagnosis. The PSA test was introduced into clinical practice two decades ago and has led to the detection of CaP at a potentially curable stage. Despite the high sensitivity of the PSA test (about 94%), a significant limitation is the very low specificity (about 20%), which is due to the fact that PSA is not a cancer-specific marker [1]. As a result, the clinical use of the PSA test has sparked controversy over the increased incidence in CaP observed in the U.S., which has led to the “over-diagnosis” and “overtreatment” of CaP [2]. A PSA level greater than/or equal to 4.0 ng/ml represents a clinical decision limit that prompts diagnostic biopsy testing [2]. However, a subset of patients with PSA levels below 4.0 ng/ml may have or will develop CaP, and a large portion (65-75%) with greater than 4.0 ng/ml may have a noncancerous prostate-related disorder [3,4]. To increase the detection sensitivity of CaP, the PSA test is used along with the DRE; however, even when used together, the specificity of the screening procedure remains low, leading to unnecessary diagnostic biopsies (65-75% of all biopsies). The prostate biopsy, which can be painful, stressful and lead to infection, is the primary method used for the diagnostic confirmation of CaP [5]. Recently a urine based PCA3 gene expression assay entered clinical practice, which displays specificity higher than serum PSA, but suffers from low sensitivity.
Therefore, developing better biomarkers will be useful in the clinical practice and reduce the number of unnecessary biopsies. New and improved diagnostic tools and methods are needed to enhance the sensitivity and specificity of current methods for the non-invasive detection of cancers in biological samples.